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Towards the Synthesis of Massadine: A Unified Strategy for the Stereoselective Synthesis of the Carbocyclic C,D‐Ring Subunit
Author(s) -
Breder Alexander,
Chinigo Gary M.,
Waltman Andrew W.,
Carreira Erick M.
Publication year - 2011
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201101862
Subject(s) - stereoselectivity , ring (chemistry) , stereochemistry , protein subunit , chemistry , combinatorial chemistry , organic chemistry , catalysis , biochemistry , gene
Massadine is a hexacyclic marine natural product, which belongs to the family of pyrrole–imidazole alkaloids. Herein, we describe a unified approach to the C,D‐ring subunit of this sponge metabolite based on the exploitation of a norbornene scaffold for the stereocontrolled construction of massadine’s carbon skeleton. Highlights of the sequence presented include the application of a stereospecific norbornyl rearrangement for facile introduction of an oxygen at the C7‐position within the norbornene nucleus, a highly regioselective and end group differentiating ozonolytic scission of a CC double bond, and an oxidative decarboxylation reaction for the installation of the hindered secondary C2‐alcohol function. Furthermore, the iterative assembly of the two guanidine entities as well as the implementation of the spirocyclic junction between the C‐ and the D‐rings are described. Collectively, these key transformations permit an entry to an appropriately functionalized carbon framework, which will serve as a starting point for our efforts toward the completion of the synthesis of massadine.